Methods and Compositions for the Treatment of Pain and Other Hormone-Allergy-Related Symptoms Using Dilute Hormone Solutions

ABSTRACT

A method and composition for the treatment of hormone allergy is disclosed. The method relates to using progesterone dilutions, or any other steroid hormone, to treat the systemic symptoms of hormone allergy, including pain. The composition of the hormone dilutions ranges from 10 −1  to 10 −5 . The hormone dilution may be administered sublingually, or, in the alternative, an intradermal route of administration may be chosen. Hormone dilutions may be administered at daily intervals or on any other treatment schedule as required to alleviate a patient&#39;s symptoms.

RELATED APPLICATION

This application claims the benefit, under 35 U.S.C. § 119(e), ofpreviously filed provisional application Methods And Compositions ForThe Treatment Of Allergy Using Dilute Hormone Solutions, Ser. No.60/332,475, filed Nov. 16, 2001.

TECHNICAL FIELD

The present invention relates in general to the treatment of pain andother hormone-allergy-related symptoms and in specific to the use of adilute hormone solution for the treatment of pain and hormone-allergysymptoms.

BACKGROUND OF THE INVENTION

Hormone allergy has been previously described in the medical literatureas premenstrual asthma. Skobeloff E. M., Spivey W. H., Silverman R. A.,Ekin B. A., Harchelroad F. P., Alessi T. V.: The effect of the menstrualcycle on asthma presentations in the emergency department. Arch InternMed 1996; 156: 1837-40. Claude F.: Asthma et menstruation. Presse Med1938; 46: 755-759; Eliasson O., Scherzer H., DeGraff A. C.: Morbidity inasthma in relation to the menstrual cycle. J Allergy Clin Immunol 1986:77: 87-94; Chandler M. H., Schuldheisz S., Phillips B., Muse K. N.:Pre-menstrual asthma: the effect of estrogen on symptoms, pulmonaryfunction, and beta 2-receptors. Pharmacology 1997; 17(2): 224-234.

Premenstrual asthma is a condition where premenstrual fluctuations inhormones such as estrogen and progesterone cause the exacerbation ofclinical symptoms. Exacerbations of symptoms appear to occur during thepremenstrual period when progesterone levels are high. Severalreferences have been made to a possible reaction to hormones. The firstreport of hormonal influence on asthma symptoms appeared in a casereport by Frank from 1931. Frank, R T: The hormonal causes ofpre-menstrual tension. Arch Neurol Psychiatry 1931; 26: 1053-57. Severeaggravation of asthma symptoms in one patient were clearly linked tooral contraceptives. Derimov, G S, Oppenheimer J: Exacerbation ofpremenstrual asthma caused by an oral contraceptive. Ann Allergy AsthmaImmunol 1998; 81: 243-46.

Skobeloff et. al reported a four-fold increase in the presentation ofasthmatic women to the emergency department during the perimenstrualinterval (days 26 to 04 of the menstrual cycle). When Skobeloff's datais superimposed over the hormone levels during the menstrual cycle, itshows that the peak emergency room visits occurred during thepremenstrual period when the progesterone is highest relative toestrogen (FIG. 1).

There has been little investigation, however, into the systemicmanifestations or treatment of hormone allergy, or the effect ofhormones on organ systems other than the female reproductive tract.While there is documentation in the literature supporting the influenceof hormones on premenstrual asthma, applicant knows of no establishedmode of action.

SUMMARY OF THE INVENTION

In accordance with teachings of the present invention, a method andcomposition for treatment of hormone allergy using steroid hormonedilutions, specifically progesterone, estrogen and testosterone isprovided.

Observations that lead to and are a part of the present invention,suggest the possibility of an allergic reaction to the steroid hormoneprogesterone as a possible cause of clinical symptoms or premenstrualasthma and other disorders.

One aspect of the present invention includes a previously unrecognizedtreatment for asthma, headache, sinus congestion, muscular pain, andbone and joint pain that involves desensitizing a body's response to itsown innate hormones. The treatment may be applied to any mammalincluding humans. In an exemplary embodiment, the mammal is female.

While hormones may fluctuate throughout the menstrual cycle, treatmentis not limited to any specific point in the menstrual cycle. In anexemplary embodiment, however, dilute solutions of progesterone areadministered sublingually, every day or every other day, as needed,until there is an alleviation of a patient's clinical symptoms. Thesedilute formulations are very similar to the type of dilutions that anallergist typically uses when treating allergic symptoms from externalsubstances, or allergens, which are foreign to the body. However, intreating a patient with hormone allergy, instead of desensitizing thepatient to a foreign substance, the patient is desensitized to his orher own innate hormone(s).

Existing clinical treatments do not generally use sublingualadministration of dilute hormone solutions to treat allergy symptoms. Inaddition, many of the symptoms that can be treated with hormonedilutions are not recognized as conventional allergy symptoms, such asbone and joint pain, muscular pain, and headache. Other symptoms whichrespond to treatment with hormone dilutions are recognized as classicallergy symptoms such as sinus congestion, ear and throat pain, eye andskin irritation.

In accordance with another aspect of the present invention, dilutions ofa hormone solution, such as progesterone are used to treat hormoneallergy symptoms. A hormone dilution ranging in concentration from 5mg/ml to 0.5 μg/ml is administered sublingually. The strength of thedilution selected for treatment may be based on the severity of thepatient's symptoms and prior treatment history. The amount, frequencyand strength of the hormone dilution may be varied depending on severityof symptoms and on response achieved.

In an alternative embodiment of the invention, the route ofadministration may be intradermal.

In accordance with a further aspect of this invention a diluteprogesterone solution (concentration 5 mg/ml to 0.5 μg/ml) or a diluteestrogen solution (concentration 5 mg/ml to 0.5 μg/ml) may beadministered to treat hormone allergy symptoms in females.

In accordance with another aspect of this invention a dilutetestosterone solution (concentration 5 mg/ml to 0.5 μg/ml) may be usedto treat allergy symptoms in males. Other steroid hormone solutions mayalso be used. All solutions of the present invention may be administeredin a pharmaceutically-acceptable carrier.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete and thorough understanding of the present invention andadvantages thereof may be acquired by referring to the followingdescription taken in conjunction with the accompanying drawings, inwhich like reference numbers indicate like features, and wherein:

FIG. 1 illustrates the number of female asthmatic patient visits to anemergency department during the menstrual cycle; and

FIG. 2 illustrates spirometry results of a patient before and aftertreatment with a dilute steroid hormone composition incorporatingteachings of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a treatment of systemic allergicmanifestations and pain caused at least in part by steroid hormones.Such manifestations have been observed and treated in female patients.For the condition of acute asthma alone, data on 83 patients treatedwith dilute progesterone has been collected. Measuring symptom responserate on a 10-point scale, a response rate of 93% overall was observed.The average reduction in symptom severity on the 10-point scale was 3.1points. The present data show a 57% reduction in symptoms on average.These results are statistically significant at a level of p<0.0001.

A composition of the present invention may include a standard solutionof aqueous progesterone, or any other indicated steroid hormone, dilutedwith normal saline to achieve concentrations of 5 mg/ml to 0.5 μg/ml.The strength of a dilution selected for treatment may be based on aseverity of the patient's symptoms and prior treatment history. Thisselection methodology may be similar to that used in treatments withforeign allergens and appropriate selections for an individual patientwill be apparent to one skilled in the art.

Typically, 0.1 cc of a hormone dilution (0.5 mg-0.05 μg per dose) isadministered sublingually every other day. The frequency ofadministration may be increased to every day or more often, as required,to achieve a desired treatment response. The strength of the hormonedilution selected for treatment may also be varied depending on severityof symptoms and on response achieved. Response to therapy may bemeasured on a 10-point scale of symptom severity as reported by apatient to a clinical provider. Additional tests for abatement ofsymptoms may also be used. Treatment of hormone allergy symptoms maycontinue for months or years as indicated by each patient's clinicalcondition.

In an alternative embodiment of this invention, the dilution may beadministered intradermally for instance, in patients who may have noresponse to sublingual drops or are unable to use the sublingualdelivery method.

EXAMPLES Example 1 Dilution Protocol

Progesterone USP 50 mg/ml (Schein Laboratories, Florham, N.J.) isdiluted with physiologically-compatible (normal) saline to produce theprogesterone dilutions used in treatments. The initial progesterone issuspended in sesame oil. Therefore, to achieve an even suspension, thevial must be vigorously shaken at each stage of the initial preparationand before use of each vial. The first dilution is made by adding 0.5 mlof progesterone to 4.5 ml normal saline. This results in a 1:10 dilutionof progesterone (progesterone 5 mg/ml) which is labeled “PROG 1.” Aftervigorously shaking the PROG 1 vial, 0.5 ml is withdrawn and injectedinto the next vial of 4.5 ml of normal saline. This results in a 1:100dilution of Progesterone (0.5 mg/ml, “PROG 2”). To produce the nextdilution, a vial of PROG 2 is immediately withdraw 0.5 ml and injectedinto the next vial of 4.5 ml of normal saline. This results in a 1:1000dilution of Progesterone (50 μg/ml “PROG 3”). These steps are repeateduntil there are five serial dilutions labeled “PROG 1” through “PROG 5.”(See Table 1). A milligram (mg) is defined as 1/1000 or 10⁻³ of a gram.A microgram (μg) is defined as 1/1,000,000 or 10⁻⁶ of a gram. TABLE 1Progesterone Dilutions Dosage Progesterone Used Label ConcentrationDilution (.1 ml) PROG 1 5 mg/ml 10⁻¹ .5 mg PROG 2 .5 mg/ml 10⁻² .05 mgPROG 3 50 μg/ml 10⁻³ 5 μg PROG 4 5 μg/ml 10⁻⁴ .5 μg PROG 5 .5 μg/ml 10⁻⁵.05 μg

Example 2 Treatment Protocol

Before beginning treatment, all of a patient's symptoms are assessed andassigned a numerical value by the patient, based on a 10-point scale.Drops are administered to a patient in a standard sequence, startingwith plain normal saline (NS) to assess the placebo effect. After plainnormal saline, PROG 5 is administered, followed by PROG 3, and then PROG1.

After the drops are placed under a patient's tongue, the patient isinstructed not to swallow for 5 seconds. Then the patient is asked toswallow the drops. After an additional 15 seconds, the patient is askedto note any change in any symptoms. The patient is questioned about eacharea of possible symptoms whether they are initially complained of ornot. The question is always asked in the same manner, “Are your symptomsworse, unchanged, or better?” The question is asked in this way toalways give the patient the option of selecting “worse” or “unchanged”before “better.” This is designed to minimize the power of suggestion or“placebo” effect.

If all of the symptoms disappear completely after the placebo, theresults are recorded and no further treatment is administered. If at anypoint, all the symptoms are relieved, the tests are concluded and thepatient is provided with a vial with the same dilution of progesteronedrops that relieved the symptoms. The patient is instructed to use thedrops as often as needed. If symptom relief does not last 12-24 hours,this is an indication that the patient needs a vial one dilutionstronger than what she is currently using.

Patients are questioned about each of twelve standard categories ofdiscomfort (see Table 2). If patients are only asked generally todescribe their symptoms they will often omit symptoms that are notincluded in their chief complaint but that they are experiencingconcomitantly with the chief complaint. The patient is asked to gradethe symptoms on a scale of 1 to 10. “Zero” is no symptoms at all and“ten” is the most intense discomfort the patient has experienced with asymptom. TABLE 2 Standard Template for Recording Response toProgesterone Dilutions Symptom Normal Location Saline PROG 5 PROG 3 PROG1 Neck Nose Eyes Throat Shortness of Breath Headache Skin Ears Back HipsLower Extremity Upper Extremity Other

The symptoms in Table 2 are defined as follows: “neck” refers tomusculoskeletal pain in the neck, “nose” refers to blockage orstuffiness in the nose, “eyes” refers to irritation such as burning oritching, “shortness of breath” is defined as a patient's perception ofthe inability to take a deep breath, “headache” refers to pain in thehead region, “skin” is defined as itching, burning or a rash on theskin, “ears” refers to pain or pressure in the ears, “back,” “hips,”“lower extremity” and “upper extremity” all refer to pain in those areasincluding arthritis-type pain or pain from chronic or acute injury.

Example 3 Treatment Response

Data has been gathered on the clinical response to dilute progesteronetherapy for over 300 patients. Patients presenting for treatment rangedin age from 30 to 70 years old and were predominantly female. See Table3. TABLE 3 Patient Demographics Age Range 30-70 years Male:Female 1:4Progesterone Dosage 0.5 mg-.05 μg Length of Treatment 1-90 days

Patients generally responded favorably in the areas of both allergy andpain symptoms. In the area of allergy symptoms, 66-87% of patientsresponded depending on the site of allergy symptoms. See Table 4. TABLE4 Response to Treatment - Allergy Symptoms (N = 300) # of % SitePatients Responders Improvement % Responders Nose 109 89 63% 82% Eyes 9073 57% 81% Throat 92 70 64% 76% Ear 35 23 52% 66% Skin 34 27 74% 79%Asthma/SOB 142 124 67% 87%

In the area of pain symptoms, 72-92% of patients responded depending onsite of pain symptoms. See Table 5. Over half of the total patients inboth groups responded with symptom relief in excess of 60%. TABLE 5Response to Treatment - Pain Symptoms (N = 300) No. of Percent PercentSite Patients Responders Improvement Responders Neck 144 104 62% 72%Headache 103 84 69% 82% Back 57 57 72% 82% Hips 26 24 79% 92% Arm 61 4876% 79% Leg 50 40 75% 80%

Progesterone antibody levels (immunoglobulins-IgG and IgM) have alsobeen measured (Immunosciences Lab, Beverly Hills, Calif.) and are higherthan normal range in approximately 70% of patients before treatment.

Example 4 Improvement in Shortness of Breath

Spirometry was performed on 22 patients with shortness of breath whowere treated with dilute progesterone drops. All 22 had improvement inspirometry with hormonal allergy treatment. An example of theimprovement is shown in FIG. 2 which shows rate of air flow and lungvolume in an individual patient pre- and post-treatment. Both the rateof air exchange (FIG. 2A, F(L/S)=air flow in liters per second) and thelung volume (FIG. 2B, V(L)=lung volume in liters, LLN=lower limits ofnormal for lung volume) of a female patient improved after diluteprogesterone treatment in accordance with teachings of the presentinvention.

Although the present invention has been described with respect tospecific preferred embodiments thereof, various changes andmodifications may be suggested to one skilled in the art and it isintended that the present invention encompass such changes andmodifications within the scope of the appended claims.

1. A method for treating at least one symptom of a hormone allergycomprising administering sublingually to a patient in need an effectiveamount of a hormone dilution to treat the at least one symptom selectedfrom the group consisting of shortness of breath, nasal congestion, eyeirritation, headache, pain in the head, neck, shoulders, back, arms,legs and joints and any combination thereof.
 2. The method of claim 1wherein the hormone dilution comprises a steroid hormone solution with aconcentration between approximately 5 mg/ml and 0.5 μg/ml.
 3. The methodof claim 2 further comprising the dilution of progesterone used to treatbone or joint pain.
 4. The method of claim 2 further comprising theconcentration of the hormone solution selected from the group consistingof 5 mg/ml, 0.5 mg/ml, 50 μg/ml, 5 μg/ml, and 0.5 μg/ml.
 5. The methodof claim 1 wherein the hormone dilution comprises an estrogen solutionwith a concentration between approximately 5 mg/ml and 0.5 μg/ml.
 6. Themethod of claim 1 wherein the dilution comprises a progesterone solutionwith a concentration approximately between approximately 5 mg/ml and 0.5μg/ml.
 7. The method of claim 6 further comprising the amount ofprogesterone administered ranges from between approximately 0.5 mg to0.05 μg per dose.
 8. The method of claim 1 wherein the dilutioncomprises a testosterone solution with a concentration betweenapproximately 5 mg/ml and 0.5 μg/ml.
 9. The method of claim 1 whereinthe at least one symptom comprises: headache, muscular pain in the head,neck, shoulders, back or legs, sinus symptoms, bone or joint pain, orany combination thereof.
 10. The method of claim 1 further comprisingadministering the hormone dilution every day, every other day or asoften as needed to alleviate symptoms.
 11. A method for treating ahormone allergy comprising: administering a dilution of progesteronewith a concentration ranging between approximately 5 mg/ml to 0.5 μg/ml;administering the dose sublingually to a patient; and administeringadditional dilutions of progesterone as often as necessary to stimulatean effective response.
 12. The method of claim 11 further comprisingtreating a symptom selected from the group consisting of shortness ofbreath, nasal congestion, eye irritation, headache, pain in the head,neck, shoulders, back, arms, legs and joints and any combinationthereof.
 13. A method of blocking pain perception in a patient's braincomprising administering sublingually a dilute hormone solution with aconcentration between approximately 5 mg/ml and 0.5 μg/ml of thehormone.
 14. The method of claim 13 wherein the hormone solutioncomprises dilute progesterone.
 15. The method of claim 13 wherein thehormone solution comprises dilute estrogen.
 16. The method of claim 13wherein in the hormone solution comprises dilute testosterone.
 17. Amethod of determining an appropriate sublingual steroid hormone dilutionfor treatment of a hormone allergy comprising: ranking the severity ofat least one symptom; administering sublingually increasingconcentrations of a dilute hormone solution to a patient; ranking theseverity of the at least one symptom again after sublingualadministration of each concentration of the steroid hormone dilution;each concentration of the steroid hormone dilution between approximately5 mg/ml and 0.5 μg/ml; and the concentration at which symptoms improveor are alleviated corresponding with an appropriate dose for arespective patient.
 18. The method of claim 17 wherein the steroidhormone comprises progesterone.
 19. The method of claim 17 furthercomprising ranking the symptom using a numeric scale.
 20. The method ofclaim 17 further comprising the increasing concentrations of hormonedilution from approximately between 0.5 μg/ml, 5 μg/ml, 50 μg/ml, 0.5mg/ml, and 5 mg/ml.
 21. A composition for the treatment of hormoneallergy comprising: a hormone solution having a concentration betweenapproximately 0.5 μg/ml and 5 mg/ml; the hormone solution including atleast normal saline; and the hormone solution operable to treat asymptom from a group consisting of shortness of breath, nasalcongestion, eye irritation, headache, pain in the head, neck, shoulders,back, arms, legs and joints and any combination thereof.
 22. Thecomposition of claim 21 wherein the hormone comprises progesterone. 23.The composition of claim 21 wherein the hormone comprises testosterone.24. A composition for the treatment of hormone allergy comprising: ahormone solution with a concentration between approximately 0.5 μg/mland 5 mg/ml; the hormone solution operable to be administeredsublingually; the hormone solution operable to treat at least onesymptom from a group consisting of shortness of breath, nasalcongestion, eye irritation, headache, pain in the head, neck, shoulders,back, arms, legs and joints and any combination thereof; and severity ofthe symptom ranked before treatment by a patient.
 25. The composition ofclaim 24 wherein the hormone comprises progesterone.
 26. The compositionof claim 24 wherein the hormone comprises testosterone.
 27. Thecomposition of claim 24 comprising the at least one symptom ranked witha numeric scale.
 28. A method for treating pain comprising:administering a dilution of progesterone with a concentration rangingfrom between approximately 5 mg/ml to 0.5 μg/ml; administering the dosesublingually to a patient; and administering additional dilutions ofprogesterone as often as necessary to stimulate an effective response.29. The method of claim 28 further comprising treating a symptomselected from the group consisting of shortness of breath, nasalcongestion, eye irritation, headache, pain in the head, neck, shoulders,back, arms, legs and joints and any combination thereof.
 30. A method ofdetermining an appropriate sublingual steroid hormone dilution fortreatment of pain comprising: ranking the severity of at least onesymptom; administering sublingually increasing concentrations of adilute hormone solution to a patient; ranking the severity of the atleast one symptom again after sublingual administration of eachconcentration of the steroid hormone dilution; each concentration of thesteroid hormone dilution between approximately 5 mg/ml and 0.5 μg/ml;and the concentration at which symptoms improve or are alleviatedcorresponding with an appropriate dose for a respective patient.
 31. Themethod of claim 30 wherein the steroid hormone comprises progesterone.32. The method of claim 30 further comprising ranking the symptom usinga numeric scale.
 33. The method of claim 30 further comprising theincreasing concentrations of hormone dilution from approximately between0.5 μg/ml, 5 μg/ml, 50 μg/ml, 0.5 mg/ml, and 5 mg/ml.
 34. The method ofclaim 30 further comprising the amount of progesterone administeredranges from between approximately 0.5 mg to 0.05 μg.
 35. A method fortreating at least one symptom of a hormone allergy comprisingadministering sublingually to a patient in need an effective amount of ahormone dilution, wherein the at least one symptom is selected from thegroup consisting of shortness of breath, nasal congestion, eyeirritation, headache, pain in the head, neck, shoulders, back, arms,legs and joints and any combination thereof and wherein relief of the atleast one symptom occurs in about 20 seconds after administration.
 36. Amethod for treating at least one symptom of a hormone allergy comprisingadministering sublingually to a subject about 0.1 milliliter of a 0.05milligram per milliliter dilution of a hormone selected from the groupconsisting of estrogen and progesterone, wherein the at least onesymptom is selected from the group consisting of shortness of breath,nasal congestion, eye irritation, headache, pain in the head, neck,shoulders, back, arms, legs and joints and any combination thereof,wherein relief of the at least one symptom occurs in about 20 secondsafter administration, and wherein the subject experiences at least abouta 57% reduction in the at least one symptom on average.
 37. A method fortreating at least one symptom of a hormone allergy comprisingadministering sublingually to a subject about 0.1 milliliter of a 0.05milligram per milliliter dilution of a hormone selected from the groupconsisting of estrogen and progesterone, wherein the at least onesymptom is selected from the group consisting of shortness of breath,nasal congestion, eye irritation, headache, pain in the head, neck,shoulders, back, arms, legs and joints and any combination thereof,wherein relief of the at least one symptom occurs in about 20 secondsafter administration and lasts for at least about twelve to abouttwenty-four hours.
 38. A method for treating at least one symptom of ahormone allergy comprising administering sublingually to a patient inneed an effective amount of a hormone dilution, wherein the at least onesymptom comprises shortness of breath, wherein relief of the at leastone symptom occurs in about 20 seconds after administration, and whereinthe subject's air flow, lung volume, or both air flow and lung volumeare higher after treatment.